Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria

J Agric Food Chem. 2024 Sep 25;72(38):20831-20841. doi: 10.1021/acs.jafc.4c03976. Epub 2024 Sep 16.

Abstract

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 μg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 μg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

Keywords: Botrytis cinerea; antimicrobial activity; isocryptolepine; structure–activity relationship.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Botrytis* / drug effects
  • Botrytis* / growth & development
  • Drug Design*
  • Fungicides, Industrial* / chemical synthesis
  • Fungicides, Industrial* / chemistry
  • Fungicides, Industrial* / pharmacology
  • Malus / chemistry
  • Malus / microbiology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Plant Diseases* / microbiology
  • Structure-Activity Relationship

Substances

  • Fungicides, Industrial
  • Anti-Bacterial Agents

Supplementary concepts

  • Botrytis cinerea